This laboratory analyzes mechanisms which control the expression of differentiated genes in hematopoietic cells. A system for the isolation of hybrid mouse erythroleukemia (MEL) cells which have retained human chromosome 16 (bearing the human alpha globin (HAG) gene) has been used to show that full expression of this gene occurs if the human donor cells are erythroid. We have also activated the expression of human globin genes from non-erythroid hematopoietic cells using a tetraploid recipient MEL cell. Analyses of hybrid donor cells of different epigenotypes and of cells from patients with non-deletion alpha thalassemia have been carried out. Expression in the hybrid MEL cells is being correlated with restriction mapping of the DNA to identify precisely the molecular basis of hematopoietic differentiation. A human myelocytic leukemia cell (HL60) has been characterized with respect to the sequence of appearance of differentiated phenotypes during exposure to dimethylformamide. A mutant of HL60 will be used in fusion experiments to delineate the genetics of myeloid differentiation. A study of the types of differentiated markers present in the secondary granules of normal granulocytes, and at different stages of myeloid maturation, is being carried out in order to further clarify the defect present in human leukemic cells.